United airways disease (UAD) is the concept that the upper and lower airways, which are anatomically and immunologically related, form a single organ. According to this concept, upper and lower airway diseases are frequently comorbid because they reflect manifestations of a single underlying disease at different sites of the respiratory tract. Allergic asthma-allergic rhinitis is the archetypal UAD, but emerging data indicate that UAD is a heterogeneous condition and consists of multiple phenotypes (observable clinical characteristics) and endotypes (pathobiologic mechanisms). The UAD paradigm also extends to myriad sinonasal diseases (eg, chronic rhinosinusitis with or without nasal polyps) and lower airway diseases (eg, bronchiectasis, chronic obstructive pulmonary disease). Here, we review currently known phenoendotypes of UAD and propose a "treatable traits" approach for the classification and management of UAD, wherein pathophysiological mechanisms and factors contributing to disease are identified and targeted for treatment. Treatable traits in UAD can be analyzed according to a framework comprising airway inflammation (eosinophilic, neutrophilic), impaired airway mucosal defense (impaired mucociliary clearance, antibody deficiency), and exogenous cofactors (allergic sensitizers, tobacco smoke, microbes). Appreciation of treatable traits is necessary in advancing the effort to deliver precise treatments and achieve better outcomes in patients with UAD.

BackgroundSevere asthma is a largely heterogeneous disease with varying phenotypic profiles. The relationship between specific allergen sensitization and asthma severity, particularly in Asia, remains unclear. We aim to study the prevalence of specific allergen sensitization patterns and investigate their association with outcomes in a severe asthma cohort in an Asian setting.MethodsWe conducted a cross-sectional study of patients receiving step 4 or 5 Global Initiative for Asthma treatment. Univariate and multivariate analyses were performed to assess the association between sensitization to a specific identifiable allergen by skin prick test (SPT) and uncontrolled asthma (defined in our study as the use of ≥2 steroid bursts or hospitalization in the past year, a history of near-fatal asthma or evidence of airflow obstruction on spirometry).ResultsTwo hundred and six severe asthma patients (mean age 45±17 years, 99 [48.1%] male) were evaluated. Of them, 78.2% had a positive SPT to one or more allergens. The most common allergen to which patients were sensitized was house dust mites (Blomia tropicalis, Dermatophagoides pteronyssinus and Dermatophagoides farinae). Also, 11.7% were sensitized to Aspergillus species. On multivariate analysis, Aspergillus sensitization was associated with uncontrolled asthma (odds ratio 6.07, 95% confidence interval 1.80–20.51). In particular, Aspergillus sensitization was independently associated with the use of ≥2 steroid bursts in the past year (odds ratio 3.05, 95% confidence interval 1.04–8.95). No similar associations of uncontrolled asthma with sensitization to any other allergens were found.ConclusionHigh allergen, specifically Aspergillus sensitization was observed in the Asian population with severe asthma by SPT. Aspergillus sensitization was specifically associated with frequent exacerbations and a greater corticosteroid requirement. An improved understanding of the severe asthma with Aspergillus sensitization phenotype is warranted, which is likely a subgroup of severe asthma with fungal sensitization.

BackgroundAssessing future risk of exacerbations is an important component of asthma management. Existing studies have investigated short‐ but not long‐term risk. Problematic asthma patients with unfavorable long‐term disease trajectory and persistently frequent severe exacerbations need to be identified early to guide treatment.AimTo identify distinct trajectories of severe exacerbation rates among “problematic asthma” patients and develop a risk score to predict the most unfavorable trajectory.MethodsSevere exacerbation rates over five years for 177 “problematic asthma” patients presenting to a specialist asthma clinic were tracked. Distinct trajectories of severe exacerbation rates were identified using group‐based trajectory modeling. Baseline predictors of trajectory were identified and used to develop a clinical risk score for predicting the most unfavorable trajectory.ResultsThree distinct trajectories were found: 58.5% had rare intermittent severe exacerbations (“infrequent”), 32.0% had frequent severe exacerbations at baseline but improved subsequently (“nonpersistently frequent”), and 9.5% exhibited persistently frequent severe exacerbations, with the highest incidence of near‐fatal asthma (“persistently frequent”). A clinical risk score composed of ≥2 severe exacerbations in the past year (+2 points), history of near‐fatal asthma (+1 point), body mass index ≥25kg/m2 (+1 point), obstructive sleep apnea (+1 point), gastroesophageal reflux (+1 point), and depression (+1 point) was predictive of the “persistently frequent” trajectory (area under the receiver operating characteristic curve: 0.84, sensitivity 72.2%, specificity 81.1% using cutoff ≥3 points). The trajectories and clinical risk score had excellent performance in an independent validation cohort.ConclusionsPatients with problematic asthma follow distinct illness trajectories over a period of five years. We have derived and validated a clinical risk score that accurately identifies patients who will have persistently frequent severe exacerbations in the future.

Chronic obstructive pulmonary disease accounts for a large burden of lung disease. It can 'overlap' with other respiratory diseases including bronchiectasis, fibrosis and obstructive sleep apnea (OSA). While COPD alone confers morbidity and mortality, common features with contrasting clinical outcomes can occur in COPD 'overlap syndromes'. Areas covered: Given the large degree of heterogeneity in COPD, individual variation to treatment is adopted based on its observed phenotype, which in turn overlaps with features of other respiratory disease states such as asthma. This is coined asthma-COPD overlap syndrome ('ACOS'). Other examples of such overlapping clinical states include bronchiectasis-COPD ('BCOS'), fibrosis-COPD ('FCOS') and OSA-COPD ('OCOS'). The objective of this review is to highlight similarities and differences between the COPD-overlap syndromes in terms of risk factors, pathophysiology, diagnosis and potential treatment differences. Expert commentary: As a consequence of COPD overlap syndromes, a transition from the traditional 'one size fits all' treatment approach is necessary. Greater treatment stratification according to clinical phenotype using a precision medicine approach is now required. In this light, it is important to recognize and differentiate COPD overlap syndromes as distinct disease states compared to individual diseases such as asthma, COPD, fibrosis or bronchiectasis.